Biomedical subjects

T E Dahms

Publications and source records attributed to T E Dahms.

At least 37 records · Page 2Linked to original sources

PubMed1993

Platelet-activating factor induces selective pulmonary arterial hyperreactivity in isolated perfused rabbit lungs.

The role of vasoreactivity in PAF-induced pulmonary hypertension (PHT) was assessed in isolated, perfused rabbit lungs. We evaluated the steady-state pulmonary vascular response to five vasoconstrictors: PGF2 alpha, norepinephrine, angiotensin II, PAF, and KCl. Pulmonary arterial pressure and pulmonary vascular resistance (PVR) were significantly greater in lungs of rabbits treated with PAF for 28 days than in control rabbits in response to PGF2 alpha and norepinephrine. When resistance was partitioned by the vascular occlusion method, at baseline the vascular resistance was equally distributed between arterial and venous segments in both experimental groups. Arterial resistance accounted for approximately 76% of PVR during norepinephrine injection and 60% of PVR during PGF2 alpha injection in PAF-treated lungs. Whereas arterial resistance accounted for approximately 63% of PVR during norepinephrine injection and 52% of PVR during PGF2 alpha injection in control lungs, there was no significant difference in the response to angiotensin II, acute PAF, and KCl in lungs from chronic PAF-treated rabbits compared with responses in control rabbit lungs, though the pressor response to acute PAF tended to be blunted in PAF-treated lungs. Chronic PAF treatment results in enhanced pulmonary arterial reactivity to selected autacoids in isolated perfused lungs.

Angiotensin II↗

PubMed1993

Effect of hydroxyethyl starch on alveolar flooding in acute lung injury in dogs.

The efficacy of hydroxyethyl starch (HES) in limiting alveolar flooding after acute lung injury was investigated using ethchlorvynol (ECV)-induced low pressure pulmonary edema in dogs. Harvested autologous plasma (PL) (control, n = 8) or 6% HES (n = 8) was infused (25 ml/kg) along with packed cells to result in an isovolemic, normochromic preparation before the administration of ECV. Extravascular thermal volume significantly increased after ECV administration in both groups of animals (6.6 to 13.4 ml/kg in PL, 6.5 to 15.0 ml/kg in HES). Systemic arterial PO2 decreased from 216 +/- 4 to 113 +/- 20 mm Hg, and venous admixture increased from 2.8 to 12.8% in the PL group but was not significantly changed in the HES group (219 +/- 5 to 203 +/- 8 mm Hg, and 2.9 to 4.4%, respectively). Epithelial lining fluid volumes after ECV administration increased in both groups but were elevated in the PL group to a greater extent than in the HES group (13.5 ml in HES versus 24.8 ml in PL). In the HES group there appeared to be no difference in the ability of plasma proteins to move across the alveolar epithelium. These results suggest that HES attenuates the flooding of the alveolar space and the resulting alterations in gas exchange during the development of low pressure pulmonary edema. The replacement of the plasma proteins with HES and the apparent inability of HES to cross the epithelial barrier into the alveoli may account for the protective effect of HES in these experiments.

Acute Disease↗

PubMed1992

Rapid separation of creatine, phosphocreatine and adenosine metabolites by ion-pair reversed-phase high-performance liquid chromatography in plasma and cardiac tissue.

A rapid ion-pair reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous detection of creatine, phosphocreatine, hypoxanthine, inosine, adenosine, AMP, ADP, ATP, 8-azaguanine, 2-chloroadenosine, and 2'-O-methyladenosine. This method has proven useful for measuring changes in nucleotide concentrations in both heart tissue and plasma samples. Separation of the compounds of interest is achieved in less than 8 min with re-equilibration in 7 min, making the total run time 15 min. Separation is performed on a 3-microns Ultrasphere ODS column employing tetrabutylammonium phosphate as the ion-pair agent and dipotassium hydrogenphosphate as the counter ion. The accuracy, rapid separation, and re-equilibration time make this method particularly useful for the routine analysis of a large number of samples.

Adenosine↗

PubMed1992

Hypercarbia during carbon dioxide pneumoperitoneum.

Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with carbon dioxide (CO2) pneumoperitoneum may retain CO2 resulting in clinically significant respiratory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after initial treatment under general anesthesia, mechanical ventilation was adjusted to maintain the end-tidal CO2 (ETCO2) at 40 mm Hg during baseline and pneumoperitoneum physiologic monitoring periods. Utilizing an analysis of variance, hemodynamic and respiratory physiologic parameters were compared. In this canine model, all dogs demonstrated consistent hypercarbia during CO2 pneumoperitoneum prior to papain treatments, but CO2 retention was significantly increased in the emphysematous state. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ETCO2 monitoring as was revealed by an increased PaCO2 (arterial carbon dioxide pressure)-ETCO2 gradient with an increasing time interval between papain exposure and period of physiologic monitoring. Irrespective of the pulmonary condition of the dog, helium pneumoperitoneum did not produce any hypercarbic or acidic changes when compared with the concomitant baseline period of dogs prior to the induction of pneumoperitoneum, thus suggesting that helium pneumoperitoneum may be a reasonable alternative in patients at risk for CO2 retention.

Acidosis, Respiratory↗

PubMed1992

Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution.

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.

Animals↗

PubMed1992

Mechanisms of pulmonary vasoconstriction induced by chemotactic peptide FMLP in isolated rabbit lungs.

The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been shown to constrict both bronchial and coronary vascular smooth muscle through the action of cyclooxygenase or lipoxygenase products. We observed that intravenous FMLP increased pulmonary vascular resistance (PVR) in isolated buffer-perfused rabbit lungs. FMLP increased the PVR (primarily in the middle segment of the pulmonary vascular bed) at concentrations greater than or equal to 10(-7) M. Maximum vasoconstriction occurred at 5 min and then slowly declined to a level that remained above baseline at 30 min. Tachyphylaxis was observed in response to FMLP. When polymorphonuclear leukocytes (PMNs) were added to the perfusate, FMLP caused a greater increase in PVR. PMN depletion with dimethylmyleran significantly reduced the PVR response to FMLP. Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate and ibuprofen, and the leukotriene synthesis blocker MK 886 had no effect on the FMLP-induced vasoconstriction. However, the reactive oxygen species scavenger catalase significantly reduced the vasoconstriction. These results suggest that FMLP induces vasoconstriction that is dependent on PMNs and mediated by reactive oxygen species with no involvement of cyclooxygenase or lipoxygenase products.

Animals↗

PubMed1992

Cyclooxygenase inhibition prevents PMA-induced increase in pulmonary vascular permeability to albumin.

In a previous study, we demonstrated that phorbol myristate acetate-(PMA) induced injury in isolated blood-perfused rabbit lungs was characterized by increased pulmonary vascular resistance (PVR) and permeability to water as measured by fluid filtration coefficient (Kf). The Kf increase was prevented by pretreatment with three cyclooxygenase inhibitors, indomethacin, ibuprofen, and meclofenamate. Other studies have shown that PMA causes a decrease in pulmonary vascular surface area, probably due to the increase in arterial resistance. Measurement of Kf requires increased microvascular pressure, and therefore Kf estimates the permeability of the entire vascular bed. Thus the permeability of the flowing vessels may be overestimated by Kf. In this study, we chose to investigate the effect of PMA on vascular permeability to protein by measuring albumin leak. Because this measurement does not require a hydraulic stress, it is more likely to reflect the permeability of flowing vessels. PMA administration (5 x 10(-8) M) caused significant increases in both PVR and 125I-labeled bovine serum albumin leak. Cyclooxygenase inhibition with indomethacin, ibuprofen, or meclofenamate prevented the PMA-induced increase in albumin leak without affecting the PVR increase. These results suggest that cyclooxygenase-mediated products of arachidonic acid mediate the PMA-induced increase in vascular permeability to both water and protein.

Albumins↗

PubMed1992

Mechanisms of increased pulmonary microvascular permeability induced by FMLP in isolated rabbit lungs.

We observed that the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L- phenylalanine (FMLP) induced pulmonary edema when polymorphonuclear leukocytes (PMNs) were added to isolated constant-flow buffer-perfused rabbit lungs. This study was designed to test the hypothesis that PMNs activated by FMLP induced lung injury by the modulation of reactive oxygen species (ROS), cyclooxygenase products, or cysteinyl leukotrienes (LTs). Addition of FMLP alone did not increase microvascular permeability (Kf). When PMNs were added to the isolated lung, FMLP caused an 80% increase in Kf. Wet-to-dry weight ratio was also significantly increased with PMNs + FMLP compared with FMLP only. There was a significant positive correlation between total myeloperoxidase activity in lung tissue and Kf values after FMLP (30 min). Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate or ibuprofen, had no effect on the PMN + FMLP-induced increase in Kf. However, the ROS inhibitor catalase and the nonantioxidant LT synthesis blocker MK 886 inhibited the PMN + FMLP increase in Kf. Perfusate levels of LTs (LTC4, -D4, and -E4) were significantly increased from baseline values 30 min after FMLP. Both MK 886 and catalase suppressed the elevation of LTs after PMN + FMLP. These results indicate that FMLP increased a pulmonary microvascular permeability in isolated buffer-perfused rabbit lungs that is PMN dependent and mediated by LT produced possibly by a result of ROS production.

Animals↗

PubMed1992

Carbon monoxide exposure of subjects with documented cardiac arrhythmias.

The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 +/- 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 +/- 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 +/- 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. In conclusion, low levels of carbon monoxide exposure resulting in blood levels of 3.2% and 5.1% carboxyhemoglobin, as measured by gas chromatography, do not have a proarrhythmic effect on patients with coronary artery disease and frequent ventricular ectopy.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1992

Bronchoalveolar eosinophilia in random-source versus purpose-bred dogs.

Eosinophils (EOS) have been implicated in changes in airway and vascular reactivity in a variety of disease states. Analysis of cells in bronchoalveolar lavage samples from chronic, heartworm-free random-source (RS) dogs indicated higher leukocyte counts with markedly higher percent and total numbers of EOS than were present in purpose-bred (PB) animals. Bronchoalveolar lavage fluid (BALF) obtained from RS dogs had a significantly elevated total nucleated cell count: 0.8 x 10(6) vs 0.4 x 10(6) for the PB dogs. RS dogs had 24% +/- 5% and PB dogs had 3% +/- 0.7% EOS. The RS animals with elevated EOS had similar percentages of neutrophils: 4% +/- 0.6% as the PB animals. Despite aggressive anthelminthic treatment, the abnormal BALF cellular profile of the RS animals persisted even though circulating levels of EOS in this group decreased. Analysis of BALF for thromboxane B2 (TxB2) and 6-keto-prostaglandin F1(1a) (6-keto-PGF1a) indicated that only the TxB2 levels were significantly different between groups. The RS BALF TxB2 levels were 73 +/- 14 pg/ml vs 23 +/- 3 pg/ml for the PB group (P < 0.05). Regression analysis of the relationship between increasing TxB2 levels and the absolute number of EOS per milliliter of BALF obtained from the RS dogs indicated a significant correlation (r = 0.83, P < 0.0001). No difference in plasma levels of these mediators was observed. Other physiologic parameters also differed between the two groups: the RS group had significantly increased heart rates and cardiac output under baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy uses carbon dioxide, a highly diffusable gas, for insufflation. With extended periods of insufflation, patient arterial carbon dioxide levels may be adversely altered. Patients were selected for laparoscopic cholecystectomy using the same criteria as for open cholecystectomy. Twenty patients (group 1) had normal preoperative cardiopulmonary status (American Society of Anesthesiologists class I), while 10 patients (group 2) had previously diagnosed cardiac or pulmonary disease (class II or III). Demographic, hemodynamic, arterial blood gas, and ventilatory data were collected before peritoneal insufflation and at intervals during surgery. Patients with preoperative cardiopulmonary disease demonstrated significant increases in arterial carbon dioxide levels and decreases in pH during carbon dioxide insufflation compared with patients without underlying disease. Results of concurrent noninvasive methods of assessing changes in partial arterial pressures of carbon dioxide (end-tidal carbon dioxide measured with mass spectrographic techniques) may be misleading and misinterpreted because changes in partial arterial pressures of carbon dioxide are typically much smaller than changes in arterial blood levels and, unlike arterial gas measurements, do not indicate the true level of arterial hypercarbia. During laparoscopic cholecystectomy, patients with chronic cardiopulmonary disease may require careful intraoperative arterial blood gas monitoring of absorbed carbon dioxide.

Aged↗

PubMed1991

Oxygen transport during steady-state submaximal exercise in chronic hypoxia.

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1991

Cyclooxygenase inhibitors prevent ethchlorvynol-induced injury in rat and rabbit lungs.

The effect of three chemically dissimilar cyclooxygenase inhibitors on ethchlorvynol-(ECV) induced acute lung injury was studied in isolated buffer-perfused rat and blood-perfused rabbit lungs. ECV caused the microvascular fluid filtration coefficient (Kf) to increase by greater than threefold in the rat lungs and twofold in the rabbit lungs. ECV caused increased pulmonary vascular resistance (PVR) and microvascular pressure measured by the double occlusion technique (Pdo) compared with the vehicle control group in the rat experiments. However, ECV had no effect on PVR or Pdo in the rabbit experiments. Pretreatment with the cyclooxygenase inhibitors indomethacin, ibuprofen, and meclofenamate prevented the increase in microvascular permeability in both the rat and rabbit lung preparations. The cyclooxygenase inhibitors also prevented the ECV-induced PVR and Pdo increases in the rat lungs but had no effect on PVR or Pdo in the rabbit lungs. These results indicate that cyclooxygenase products of arachidonate metabolism mediate the ECV-induced Kf increase in both isolated rat and rabbit lungs.

Animals↗

PubMed1991

Vascular resistance and Kf in normal and PMA-injured rabbit lungs: effects of adenosine.

The effects of adenosine (ADO) on pulmonary vascular resistance (PVR) distribution, vascular compliance (C), and permeability were determined in normal and PMA-injured isolated rabbit lungs perfused with a 1:1 mixture of 6% albumin in Krebs-Henseleit buffer and autologous blood. ADO or vehicle was continuously infused into the reservoir at 1,4, or 5 mumol/min after a 1-mumol bolus of ADO or vehicle. The capillary filtration coefficient (Kf) and arterial, venous, and double occlusion pressures were measured at baseline and 30 min after phorbol myristate acetate (PMA; 4 x 10(-8) M) or vehicle. Perfusate differential and total leukocyte counts as well as adenine nucleotides, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) concentrations were determined at each measurement period. ADO was recovered as hypoxanthine and inosine in the perfusate. ADO alone did not alter PVR, C, Kf, or TxB2 but reduced 6-keto-PGF1 alpha levels. PMA induced an increase in Kf (0.024 +/- 0.002 to 0.040 +/- 0.006 g.cmH2O-1.min-1, P less than 0.05) that was completely blocked by 4 or 5 mumol/min ADO. PVR increased by 63 +/- 11% after PMA, primarily in the arteries and arterial and venous microvessels. The postcapillary resistance increase was blunted by 4 mumol/min ADO; 5 mumol/min ADO prevented the PVR increase in all segments. ADO did not affect the initial adherence of neutrophils in the lung or the PMA-induced 87 +/- 2% decrease in circulating leukocytes (greater than 98% lymphocytes) or threefold increase in TxB2 levels. These results suggest that protection by ADO is not mediated by the altering of cyclooxygenase products or by leukocyte adherence.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF.

The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1-1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70-90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF.

Adenosine↗

PubMed1991

Effects of carbon monoxide on myocardial ischemia.

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

Adult↗

PubMed1990

Production of leukotrienes in phorbol ester-induced acute lung injury.

Leukotrienes, when administered into the pulmonary circulation of intact animals or isolated perfused lungs, have been associated with the formation of pulmonary edema. In addition, leukotrienes were identified in edema fluid and in bronchoalveolar lavage fluid (BALF) both from patients with the adult respiratory distress syndrome (ARDS) and from dogs with ethchlorvynol-induced acute lung injury (ALI). To determine whether the identification of leukotrienes in BALF was a finding common to ALI, etiology notwithstanding, we produced acute lung injury in dogs with phorbol myristate acetate (PMA). PMA produces a model of ALI thought to differ mechanistically from ethchlorvynol-induced ALI. Leukotriene C4 (LTC4), D4 (LTD4) and B4 (LTB4) were measured in BALF before and after PMA administration in intact pentobarbital-anesthetized dogs. The intravenous administration of 20 or 30 micrograms/kg of PMA produced increases in pulmonary vascular resistance (PVR) and extravascular lung water (EVLW), whereas, 10 or 15 micrograms/kg caused only a modest increase in PVR with no increase in EVLW. LTD4 and LTB4 were increased in BALF solely in those animals that developed increases in EVLW. These results, when viewed together with those reported in humans with ARDS and in dogs with ethchlorvynol-induced ALI, support the hypothesis that leukotriene detection in BALF is a feature common to ALI, etiology notwithstanding.

Animals↗

PubMed1990

Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs.

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.

Animals↗